The purpose of this application is to create an optimal environment for pathologists - molecular biologists - clinicians to join forces with developmental biologists to re-examine the tenets of neoplasia and generate information in a developmental context. It has been established in select systems that the stem cells of neoplasms have the capacity for differentiation yielding benign progeny. This phenomenon must be studied in mesenchymal and other tumors where precise biochemical markers can be used to identify differentiation. Then modulation of the process will be attempted as an alternative to cytotoxic chemotherapy. Since differentiation is an epigenetic phenomenon, can the process of differentiation control the expression of an integrated DNA oncogenic viral genome? Then by suitable means can the repressed viral genome be depressed and transform the host cell? Chemical and viral transformed cells will be used as models of differentiation. Admittedly proximate chemical carcinogens react with DNA, RNA and protein, but which reaction is responsible for transformation? Cell to cell interactions are critical in differentiation and expression of the malignant phenotype. Our entree to this area is study at the physical chemical level of lectin binding. Finally the initial event in invasion and metastasis is penetration of basement membrane. Search will be made in normal tissues and in in situ and invasive tumors for the enzymes responsible for degradation of basement membrane.